Search Results - "Obach, R"

Pharmacologically active drug metabolites: impact on drug discovery and pharmacotherapy by Obach, R Scott

“…Metabolism represents the most prevalent mechanism for drug clearance. Many drugs are converted to metabolites that can retain the intrinsic affinity of the…”
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Linezolid Metabolism Is Catalyzed by Cytochrome P450 2J2, 4F2, and 1B1 by Obach, R Scott

“…The oxazolidinone antibacterial linezolid has been in clinical use for over 20 years, yet knowledge of the contributions of specific cytochrome (CYP) 450…”
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Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds by Lombardo, Franco, Berellini, Giuliano, Obach, R Scott

“…We report a trend analysis of human intravenous pharmacokinetic data on a data set of 1352 drugs. The aim in building this data set and its detailed analysis…”
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Disposition of Nirmatrelvir, an Orally Bioavailable Inhibitor of SARS-CoV-2 3C-Like Protease, across Animals and Humans by Eng, Heather, Dantonio, Alyssa L, Kadar, Eugene P, Obach, R Scott, Di, Li, Lin, Jian, Patel, Nandini C, Boras, Britton, Walker, Gregory S, Novak, Jonathan J, Kimoto, Emi, Singh, Ravi Shankar P, Kalgutkar, Amit S

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor PF-07321332 (nirmatrelvir), in combination with ritonavir…”
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Prediction of Human Clearance of Twenty-Nine Drugs from Hepatic Microsomal Intrinsic Clearance Data: An Examination of In Vitro Half-Life Approach and Nonspecific Binding to Microsomes by OBACH, R. S

“…Twenty-nine drugs of disparate structures and physicochemical properties were used in an examination of the capability of human liver microsomal lability data…”
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Emerging Models of Drug Metabolism, Transporters, and Toxicity by Sawant-Basak, Aarti, Obach, R Scott

“…This commentary summarizes expert mini-reviews and original research articles that have been assembled in a special issue on novel models of drug metabolism…”
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Addressing the Challenges of Low Clearance in Drug Research by Di, Li, Obach, R. Scott

“…As a result of high-throughput ADME screening, early metabolite identification, and exploration of novel chemical entities, low-intrinsic-clearance compounds…”
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Cytochrome P450 3A Time-Dependent Inhibition Assays Are Too Sensitive for Identification of Drugs Causing Clinically Significant Drug-Drug Interactions: A Comparison of Human Liver Microsomes and Hepatocytes and Definition of Boundaries for Inactivation Rate Constants by Eng, Heather, Tseng, Elaine, Cerny, Matthew A, Goosen, Theunis C, Obach, R Scott

“…Time-dependent inhibition (TDI) of CYP3A is an important mechanism underlying numerous drug-drug interactions (DDIs), and assays to measure this are done to…”
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The Drug-Drug Interaction Between Erlotinib and OSI-930 is Mediated Through Aldehyde Oxidase Inhibition by Tang, Lloyd Wei Tat, Shi, Yuanyuan, Sharma, Raman, Obach, R Scott

“…The propensity for aldehyde oxidase (AO) substrates to be implicated in drug-drug interactions (DDI) is not well-understood due to the dearth of potent…”
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Evaluation of Icotinib as a Potent and Selective Inhibitor of Aldehyde Oxidase for Reaction Phenotyping in Human Hepatocytes by Tang, Lloyd Wei Tat, DaSilva, Ethan, Lapham, Kimberly, Obach, R Scott

“…Aldehyde oxidase (AO) is a molybdenum cofactor-containing cytosolic enzyme that has gained prominence due to its involvement in the developmental failure of…”
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An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19 by Owen, Dafydd R, Allerton, Charlotte M N, Anderson, Annaliesa S, Aschenbrenner, Lisa, Avery, Melissa, Berritt, Simon, Boras, Britton, Cardin, Rhonda D, Carlo, Anthony, Coffman, Karen J, Dantonio, Alyssa, Li, Di, Eng, Heather, Ferre, RoseAnn, Gajiwala, Ketan S, Gibson, Scott A, Greasley, Samantha E, Hurst, Brett L, Kadar, Eugene P, Kalgutkar, Amit S, Lee, Jack C, Lee, Jisun, Liu, Wei, Mason, Stephen W, Noell, Stephen, Novak, Jonathan J, Obach, R Scott, Ogilvie, Kevin, Patel, Nandini C, Pettersson, Martin, Rai, Devendra K, Reese, Matthew R, Sammons, Matthew F, Sathish, Jean G, Singh, Ravi Shankar P, Steppan, Claire M, Stewart, Al E, Tuttle, Jamison B, Updyke, Lawrence, Verhoest, Patrick R, Wei, Liuqing, Yang, Qingyi, Zhu, Yuao

“…Path to another drug against COVID-19The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges…”
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Predicting clearance in humans from in vitro data by Obach, R Scott

“…The use of in vitro metabolism in scaling to predict human clearance of new chemical entities has become a commonplace activity in the research and development…”
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Cytochrome P450 3A4 mRNA is a more reliable marker than CYP3A4 activity for detecting pregnane X receptor-activated induction of drug-metabolizing enzymes by Fahmi, Odette A, Kish, Mary, Boldt, Sherri, Obach, R Scott

“…Induction of cytochrome P450 (P450) activity in the clinic can result in therapeutic failure such as tissue rejection in transplant patients or unwanted…”
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Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 670 Drug Compounds by OBACH, R. Scott, LOMBARDO, Franco, WATERS, Nigel J

“…We present herein a compilation and trend analysis of human i.v. pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly…”
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Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19 by Boras, Britton, Jones, Rhys M., Anson, Brandon J., Arenson, Dan, Aschenbrenner, Lisa, Bakowski, Malina A., Beutler, Nathan, Binder, Joseph, Chen, Emily, Eng, Heather, Hammond, Holly, Hammond, Jennifer, Haupt, Robert E., Hoffman, Robert, Kadar, Eugene P., Kania, Rob, Kimoto, Emi, Kirkpatrick, Melanie G., Lanyon, Lorraine, Lendy, Emma K., Lillis, Jonathan R., Logue, James, Luthra, Suman A., Ma, Chunlong, Mason, Stephen W., McGrath, Marisa E., Noell, Stephen, Obach, R. Scott, O’ Brien, Matthew N., O’Connor, Rebecca, Ogilvie, Kevin, Owen, Dafydd, Pettersson, Martin, Reese, Matthew R., Rogers, Thomas F., Rosales, Romel, Rossulek, Michelle I., Sathish, Jean G., Shirai, Norimitsu, Steppan, Claire, Ticehurst, Martyn, Updyke, Lawrence W., Weston, Stuart, Zhu, Yuao, White, Kris M., García-Sastre, Adolfo, Wang, Jun, Chatterjee, Arnab K., Mesecar, Andrew D., Frieman, Matthew B., Anderson, Annaliesa S., Allerton, Charlotte

“…COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of…”
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Mechanism-Based Inactivation of Human Cytochrome P450 Enzymes and the Prediction of Drug-Drug Interactions by OBACH, R. Scott, WALSKY, Robert L, VENKATAKRISHNAN, Karthik

“…The ability to use vitro inactivation kinetic parameters in scaling to in vivo drug-drug interactions (DDIs) for mechanism-based inactivators of human…”
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Nonclassical Phenyl Bioisosteres as Effective Replacements in a Series of Novel Open-Source Antimalarials by Tse, Edwin G, Houston, Sevan D, Williams, Craig M, Savage, G. Paul, Rendina, Louis M, Hallyburton, Irene, Anderson, Mark, Sharma, Raman, Walker, Gregory S, Obach, R. Scott, Todd, Matthew H

“…The replacement of one chemical motif with another that is broadly similar is a common method in medicinal chemistry to modulate the physical and biological…”
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Mechanistic Modeling to Predict Midazolam Metabolite Exposure from In Vitro Data by Nguyen, Hoa Q, Kimoto, Emi, Callegari, Ernesto, Obach, R Scott

“…Methods to predict the pharmacokinetics of drugs in humans from in vitro data have been established, but corresponding methods to predict exposure to…”
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A comprehensive listing of bioactivation pathways of organic functional groups by Kalgutkar, Amit S, Gardner, Iain, Obach, R Scott, Shaffer, Christopher L, Callegari, Ernesto, Henne, Kirk R, Mutlib, Abdul E, Dalvie, Deepak K, Lee, Jae S, Nakai, Yasuhiro, O'Donnell, John P, Boer, Jason, Harriman, Shawn P

“…The occurrence of idiosyncratic adverse drug reactions during late clinical trials or after a drug has been released can lead to a severe restriction in its…”
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Human Absorption, Distribution, Metabolism, and Excretion Studies: Origins, Innovations, and Importance by Cerny, Matthew A, Spracklin, Douglas K, Obach, R Scott

“…Human absorption, distribution, metabolism, and excretion (hADME) studies represent one of the most important clinical studies in terms of obtaining a…”
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